Method for producing 4-chlorobiphenyl and 4-chlorobiphenyl-specific specifications

ABSTRACT

The invention relates to a process for preparing 4-chlorobiphenyl by 
     (a) reacting biphenyl and chlorine in the presence of one or more ring-chlorination catalysts, and 
     (b) subjecting the reaction mixture obtained in step (a) to fractional distillation to obtain 4-chlorobiphenyl.

This application is a 371 of PCT/EP00/03945, filed May 3, 2000.

The present invention relates to a process for preparing4-chlorobiphenyl by chlorination of biphenyl, isolation of the4-chlorobiphenyl from the reaction mixture in high purity and4-chlorobiphenyl having a low 3-chlorobiphenyl content.

4-Chlorobiphenyl is an important intermediate in the preparation ofpharmaceuticals and crop protection products. It is therefore necessarythat it can be obtained in a simple manner, inexpensively and in highpurities.

Processes for preparing 4-chlorobiphenyl which require relativelycomplex precursors such as phenylboronic acid, 4-chloro-phenyl-diazoniumsalts, phenyl-magnesium bromide, 4-bromo-chlorobenzene,4-iodo-chlorobenzene, phenyl triflate, 4-bromo-biphenyl anddiphenyl-tetrazole compounds are known (cf Org. Chem., 62(10), 3405-6(1997); Nippon Kagaku Kaishi, 1997 (2), 119-26; Tetrahedron, 52(21),7201-20 (1996); Org. Chem. 57(1), 391-3 (1992) and J. Chem. Res., Synop.1994 (6), 216-7). Even if the yields are sometimes above 90% and4-chlorobiphenyl can be isolated readily in pure form and free of3-chlorobiphenyl, the precursors can be prepared only by verycomplicated processes. For this reason, these processes for preparing4-chlorobiphenyl are uneconomical and relatively unsuitable for use onan industrial scale.

Tetrahedron 52(26), 8863-6 (1996) describes the chlorination of biphenylusing 2 equivalents of tin tetrachloride and 1 equivalent of leadtetraacetate. The yield of 4-chlorobiphenyl is 70%. Nothing is saidabout the amount of 2- and 3-chlorobiphenyl formed and the degree towhich they are separated off. The use of large amounts of leadtetraacetate and tin tetrachloride makes the process costly anduneconomical.

Angew. Chem., 103(12), 1687-9 (1991) describes the chlorination ofbiphenyl catalyzed by zeolites of the structure type LTL, with thepotassium form (K-L) being mentioned as being particularly favorable.However, this publication is not directed at the preparation andisolation of 4-chlorobiphenyl, but rather the preparation and isolationof 4,4′-dichlorobiphenyl which can be crystallized from the productmixture.

It would be desirable to be able to prepare 4-chlorobiphenyl in a singlestep from biphenyl and chlorine. According to U.S. Pat. No. 1,890,427,this is possible by chlorination of biphenyl in chlorobenzene in thepresence of metallic iron as catalyst. However, this gives a mixturecomprising 4-chlorobiphenyl, 3-chlorobiphenyl, 2-chlorobiphenyl andunreacted biphenyl. The separation of this mixture is very complicated.For separating off one isomer, the reference describes crystallizationfrom noneutectic mixtures above the freezing point of the eutectic. Thismeans that separation of the entire mixture makes it necessary to carryout a complicated sequence of distillation and crystallization steps.Czech. Chem. Prum., 30(10), 529-32 (1980) confirms this. To achievepurities of greater than 99%, the latter reference describes thefollowing steps to be carried out in succession for the separation ofmixtures comprising 2-, 3- and 4-chlorobiphenyl: 1. distillation, 2.crystallization of the fractions from the distillation and 3.recrystallization of the fractions from the crystallization fromethanol.

The problems in isolating 4-chlorobiphenyl from reaction mixturesobtained in the chlorination of biphenyl explain why the complicatedsynthetic route indicated at the outset has been considered for thepreparation of pure 4-chlorobiphenyl.

There is therefore still a need for a process which allows4-chlorobiphenyl to be obtained in high purity in a simple manner frominexpensive starting compounds.

We have now found a process for preparing 4-chlorobiphenyl which ischaracterized in that biphenyl and chlorine are reacted in the presenceof ring-chlorination catalysts and the reaction mixture obtained issubjected to fractional distillation.

Suitable ring-chlorination catalysts are the catalysts known for thispurpose, e.g. the anhydrous chlorides of main groups 3, 4 and 5 and oftransition groups 3 to 10 of the Periodic Table of the Elements, alsothe anhydrous chlorides of the rare earths. Preference is given to borontrichloride, aluminum trichloride and iron trichloride. Further suitablecatalysts are heterogeneous aluminosilicates, e.g. sheet silicates suchas montmorillonite and bentonite, heterogeneous aluminosilicates havingamorphous, vitreous porous structures which can be prepared bycoprecipitation or via cogels (see, for example, Ind. Eng., Chem. Res.34, 421.33 (1995); J. F. Harrod and R. M. Laine, Applications ofOrganometallic Chemistry in the Preparation and Processing of AdvancedMaterials, Kluver Academic Publishers (1995), pp.27-46) and zeolites,e.g. those of the structure types Ω, X and L. Possible mobile ions inthese zeolites are, for example, the elements of main groups 1, 2 and 3and of transition group 3 of the Periodic Table of the Elements and therare earths. Preference is given to H, Na, K, Rb, Cs, Ca, Mg, Sr, Ba,Sc, Y, La, Ce and Pr. Particularly preferred ring-chlorination catalystsare zeolites of the structure type L, very particularly preferably ofthe type K-L in which the mobile ions are from 80 to 100%, preferablyfrom 90 to 100%, potassium ions.

The ring-chlorination catalyst can be used, for example, in amounts offrom 0.2 to 20% by weight, preferably in amounts of from 2 to 12% byweight, based on biphenyl used.

The reaction according to the invention can be carried out at, forexample, temperatures of from 0 to 120° C., preferably temperatures offrom 20 to 100° C. The pressure during the reaction according to theinvention is not critical and can be, for example, from 0.2 to 20 bar.It is preferably from 0.8 to 8 bar. Particular preference is given tocarrying out the chlorination at atmospheric pressure.

The reaction according to the invention can be carried out batchwise,semibatchwise or continuously. Suitable batch reactors are, for example,stirred vessels, bubble columns and loop reactors. If the process is tobe carried out continuously, this can be achieved by connecting aplurality of the abovementioned batch reactors in series. In principle,however, it is also possible to use residence tube reactors or reactorsemploying stationary catalyst beds.

The reaction according to the invention can be carried out in thepresence or absence of a solvent and/or a cocatalyst. Suitable solventsare, for example, aprotic solvents which do not react with chlorineunder the reaction conditions. Preference is given to chlorinatedhydrocarbons, in particular methylene chloride. A suitable cocatalystis, for example, chloroacetic acid. The chlorination according to theinvention is generally carried out in such a way that from 30 to 90%,preferably from 10 to 70%, particularly preferably from 30 to 60%, ofthe biphenyl used are reacted in a single pass.

In the process of the invention, the reaction mixture present after thechlorination is separated into its components exclusively by means of afractional distillation.

If a heterogeneous ring-chlorination catalyst, e.g. a zeolite, has beenused, this is advantageously separated off mechanically, e.g. byfiltration or centrifugation, prior to the distillation. If a solublering-chlorination catalyst such as iron trichloride has been used, thisis advantageously deactivated and separated off, e.g. by addition ofwater and removal of the aqueous phase, prior to the distillation.

Before the distillation, a base can be added to the mixture to bedistilled in order to destroy any residues having a catalytic activityand thus reliably to prevent transchlorinations during the distillation.Suitable bases for this purpose are, for example, sodium carbonate,calcium carbonate, sodium acetate and potassium hydrogencarbonate.

The columns for the fractionation of the reaction mixture from thechlorination, which may have been pretreated as described above, canhave, for example, from 5 to 500, preferably from 10 to 100,particularly preferably from 20 to 50, theoretical plates. The manner inwhich this number of theoretical plates can be achieved by means ofinternals in the column is known to those skilled in the art. Thecolumns are, for example, operated at a reflux ratio of from 1 to 30,preferably from 2 to 20.

The columns can be operated, for example, at temperatures at the bottomof from 100 to 300° C., preferably from 150 to 250° C., and at pressuresbeginning in the range from 0.5 to 3 bar and ending in the range from 3to 300 mbar, preferably from 10 to 100 mbar.

The fractional distillation can be carried out batchwise, semibatchwiseor continuously.

A continuous fractional distillation process can be carried out using,for example, three columns which are connected in series and are eachequipped with stripping sections and enrichment sections. The firstcolumn gives unreacted biphenyl at the top, the second gives2-chlorobiphenyl at the top and the third gives 4-chlorobiphenyl at thetop.

A batchwise fractional distillation can be carried out using a column ofthe above-described type which is not equipped with a stripping sectionand an enrichment section.

If a solvent, e.g. methylene chloride, has been used, this isadvantageously separated off before the actual fractional distillation,e.g. by distillation in a column installed upstream.

The chlorination according to the invention generally leads to reactionmixtures containing little 3-chlorobiphenyl. The ratio of4-chlorobiphenyl to 3-chlorobiphenyl in the reaction mixture is, forexample, above 100:1, frequently above 300:1 and particularlyadvantageously above 800:1. If it is, in an exceptional case, 100:1 orbelow, routine tests should be carried out to find a combination ofreaction conditions, catalyst and possibly solvent in the case of whichthe desired low contents of 3-chlorobiphenyl can be obtained in thereaction mixture. The fractional distillation to be carried outaccording to the invention thus always makes it possible for the3-chlorobiphenyl content of the 4-chlorobiphenyl isolated to be reducedappreciably in this way, even though the reduction may not be to belowthe detection limit.

Furthermore, the process of the invention makes it possible to obtain4-chlorobiphenyl having a purity of 99.5% or more, frequently 99.95% ormore, in a simple manner from simple starting materials and using simpleauxiliaries. It is thus well suited for further processing to producepharmaceuticals and crop protection products. The yields of4-chlorobiphenyl in the process of the invention are above 90%.

The process of the invention has for the first time made available4-chlorobiphenyl containing from 0.001 to 10‰, preferably from 0.01 to1‰ and particularly preferably from 0.03 to 0.3‰, of 3-chlorobiphenyl.It is a typical feature of the process of the invention that it gives4-chlorobiphenyl having these 3-chlorobiphenyl contents.

The present invention therefore also provides 4-chlorobiphenylcontaining from 0.001 to 10‰, preferably from 0.01 to 1‰, particularlypreferably from 0.03 to 0.3‰, of 3-chlorobiphenyl.

EXAMPLES General

a) For the quantitative determination of the components, 5% strengthsolutions of the reaction mixtures in chlorobenzene were analyzed by gaschromatography.

The detection limits were: 200 ppm of biphenyl, 100 ppm ofmonochlorobiphenyl, 400 ppm of 4,4′-dichlorobiphenyl and 400 ppm oftrichlorobiphenyls.

b) Reactor: oil-thermostated 250 ml flange pot with gas inlet tube andstirrer.

Example 1

Chlorination in Methylene Chloride

93.5 g of biphenyl together with 134 g of methylene chloride were placedin the reactor and 9 g of zeolite of the type K-L (dry) were added as afine powder. The reactor was flushed with nitrogen and introduction ofchlorine was commenced at 40° C. Details may be found in Table 1.

TABLE 1 Time of chlorine Amount Content in the reaction mixture (% byarea) Selectivity to introduction of Chlorobiphenyl 4-chlorobiphenyl(min) chlorine Biphenyl 2- 3- 4- 4,4′-di (%) 45 28.7 76.92 0.74 0.0121.59 0.58 93.54 80 47.2 61.33 1.21 0.04 35.29 1.83 91.26 108 62.8 48.941.58 0.04 45.46 3.60 90.34 125 70.5 43.22 1.76 0.06 49.79 4.74 87.69

Example 2

Chlorination in the Presence of Chloroacetic Acid

101 g of biphenyl, 2.5 g of chloroacetic acid and 10 g of zeolite of thetype K-L (dry) were placed in the reactor and the reactor was flushedwith nitrogen. The mixture was then heated to 100° C. and theintroduction of chlorine was commenced. Details may be found in Table 2.

TABLE 2 Time of chlorine Amount Content in the reaction mixture (% byarea) Selectivity to introduction of Chlorobiphenyl 4-chlorobiphenyl(min) chlorine Biphenyl 2- 3- 4- 4,4′-di (%) 240 31.8 79.55 2.51 0.0816.07 0.31 78.58 425 58.7 59.75 5.41 0.12 30.03 1.27 74.61

Example 3

Distillation (all Percentages are by Weight Unless Indicated Otherwise;CBP Represents Chlorobiphenyl).

The procedure of Example 1 was used to prepare a larger amount ofreaction mixture having the composition present in Example 1 after achlorination time of 108 minutes. The catalyst was firstly removed fromthis reaction mixture by filtration and the major part of the methylenechloride was taken off via a column. This left 2991.5 g of a mixturecomprising

7.45% of methylene chloride,

45.86% of biphenyl,

1.62% of 2-CBP,

0.12% of 3-CBP,

41.5% of 4-CBP and

3.44% of 4,4′-DICBP.

This mixture was fractionally distilled from a 41 flask as still pot viaa column having 34 theoretical plates (internal diameter: 5 cm, height:100 cm, packing: 4×4 mm wire mesh rings).

Firstly, 56.8 g of methylene chloride were obtained at atmosphericpressure and a pressure reduced down to 500 mbar, at temperatures at thebottom of from 202 to 210° C., temperatures at the top of from 39 to 24°C. and a reflux ratio of 5.

Subsequently, 1209.4 g of biphenyl were obtained at a pressure at thetop of the column of 30 mbar, at temperatures at the bottom of from 156to 178° C., at temperatures at the top of 136-137° C. and a reflux ratioof 5. This can be returned to the chlorination.

254.9 g of an intermediate fraction comprising biphenyl, 2-CBP, 3-CBPand 4-CBP were then obtained at a pressure at the top of the column of30 mbar, at temperatures at the bottom of from 178 to 179° C.,temperatures at the top of from 138 to 166° C. and a reflux ratio risingfrom 5 to 10. This fraction can be returned to the distillation.

Now, 351.6 g of a first 4-CBP fraction comprising 99.7% of 4-CBP, 0.16%of 3-CBP and less than 0.1% of 2-CBP and less than 0.1% of biphenyl wereobtained at a pressure at the top of the column of 30 mbar, atemperature at the bottom of 180° C., a temperature at the top of 166°C. and a reflux ratio of 10. This fraction can, if the specification issatisfactory, be passed on as product, if appropriate in admixture withthe second 4-CBP fraction, or, if the specification is not satisfactory,be returned to the distillation.

Finally, 675.5 g of a second 4-CBP fraction comprising above 99.95% of4-CBP and 0.03% of 3-CBP were obtained at a pressure at the top of thecolumn of 30 mbar, temperatures at the bottom of from 181 to 231° C., atemperature at the top of 166° C. and a reflux ratio of 2.

What is claimed is:
 1. A process for preparing 4-chlorobiphenylcontaining from 0.001 to 10% of 3-chlorobiphenyl comprising (a) reactingbiphenyl and chlorine in the presence of one or more ring-chlorinationcatalysts, and (b) subjecting the reaction mixture obtained in step (a)to fractional distillation to obtain 4-chlorobiphenyl.
 2. A processaccording to claim 1 wherein the ring-chlorination catalyst is ananhydrous chloride of a metal of main groups 3, 4, or 5 and/or oftransition groups 3 to 10 of the Periodic Table of the Elements, ananhydrous chloride of a rare earth metal, or an aluminosilicate.
 3. Aprocess according to claim 1 wherein the ring-chlorination catalyst is azeolite of type L having mobile ions wherein 80 to 100% of the mobileions are potassium ions.
 4. A process according to claim 1 wherein thering-chlorination catalyst is used in an amount of from 0.2 to 20% byweight, based on the biphenyl.
 5. A process according to claim 1 carriedout at temperatures of from 0 to 120° C. and pressures in the range from0.2 to 20 bar.
 6. A process according to claim 1 carried out in such away that from 30 to 90% of the biphenyl is reacted in a single pass. 7.A process according to claim 1 wherein the fractional distillation iscarried out using a column having from 5 to 500 theoretical plates andoperated at a reflux ratio in the range from 1 to
 30. 8. A processaccording to claim 1 wherein the reaction and the fractionaldistillation steps are, independently of one another, carried outbatchwise, semibatchwise, or continuously.
 9. 4-Chlorobiphenylcontaining from 0.001 to 10‰ of 3-chlorobiphenyl.
 10. 4-Chlorobiphenylaccording to claim 9 containing from 0.001 to 1‰ of 3-chlorobiphenyl.